Adult neurogenesis represents a striking form of structural plasticity in the mature mammalian brain. One hallmark of adult neurogenesis is its modulation by a plethora of external stimuli in an activity-dependent manner. For example, electroconvulsive treatment (ECT) of adult mice induces highly synchronized activation of mature dentate neurons without detectable excitotoxicity and causes sustained up-regulation of hippocampal neurogenesis and a lasting treatment for depression. How transient activation of existing neuronal circuits leads to such long lasting effects is largely unknown. Epigenetic mechanisms provide a basis for long-lasting modulation of neurogenesis, as well as mediating activity-dependent regulation of neural plasticity. Compositions and methods capable of modulating activity-dependent neural plasticity would likely be useful as neuroprotectants and for the treatment of mood disorders.